Background/Aims: P2X receptors are membrane ion channels activated by extracellular adenosine 5’- triphosphate (ATP) which contribute to various physiological processes. The present study describes in synovial fibroblasts (SFs) obtained from osteoarthritis (OA) patients and in SW 982 cells derived from human synovial sarcoma a pharmacological characterization of P2X1 and P2X3 receptors implicated in the modulation of inflammatory processes in joint diseases. Methods: mRNA, western blotting, saturation and competition binding experiments were used to characterize purinergic receptors. From a functional point of view nuclear factor B (NF-B) activation, tumour necrosis factor- (TNF-), interleukin 6 (IL-6) and prostaglandin E2 (PGE2) production were evaluated by means of enzyme-linked immunosorbent assays. Results: P2X1 and P2X3 receptors were present with high affinity and density. Selected purinergic agonists and antagonists exhibited a different thermodynamic behavior. P2X1 receptors showed an anti-inflammatory effect reducing NF-B activation and TNF- release whilst P2X3 receptors mediated opposite response. No effect was mediated by P2X1 and P2X3 receptors on IL-6 and PGE2 production. Conclusion: SFs from OA patients and SW 982 cells similarly express P2X1 and P2X3 receptors which are able to modulate in opposite way some functional responses closely associated with inflammation suggesting that purinergic receptors may represent a potential target in therapeutic antiinflammatory joint interventions.
P2X1 and P2X3 Purinergic Receptors Differentially Modulate the Inflammatory Response in Human Osteoarthritic Synovial Fibroblasts
VARANI, KatiaPrimo
;DE MATTEI, MonicaSecondo
;VINCENZI, Fabrizio;TOSI, ALICE;TARGA, Martina;PELLATI, Agnese;MASSARI, LeoPenultimo
;BOREA, Pier Andrea
Ultimo
2010
Abstract
Background/Aims: P2X receptors are membrane ion channels activated by extracellular adenosine 5’- triphosphate (ATP) which contribute to various physiological processes. The present study describes in synovial fibroblasts (SFs) obtained from osteoarthritis (OA) patients and in SW 982 cells derived from human synovial sarcoma a pharmacological characterization of P2X1 and P2X3 receptors implicated in the modulation of inflammatory processes in joint diseases. Methods: mRNA, western blotting, saturation and competition binding experiments were used to characterize purinergic receptors. From a functional point of view nuclear factor B (NF-B) activation, tumour necrosis factor- (TNF-), interleukin 6 (IL-6) and prostaglandin E2 (PGE2) production were evaluated by means of enzyme-linked immunosorbent assays. Results: P2X1 and P2X3 receptors were present with high affinity and density. Selected purinergic agonists and antagonists exhibited a different thermodynamic behavior. P2X1 receptors showed an anti-inflammatory effect reducing NF-B activation and TNF- release whilst P2X3 receptors mediated opposite response. No effect was mediated by P2X1 and P2X3 receptors on IL-6 and PGE2 production. Conclusion: SFs from OA patients and SW 982 cells similarly express P2X1 and P2X3 receptors which are able to modulate in opposite way some functional responses closely associated with inflammation suggesting that purinergic receptors may represent a potential target in therapeutic antiinflammatory joint interventions.File | Dimensione | Formato | |
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